Study on AZN’s Seroquel Might Have Warned Pentagon Off Big Use of Iffy PTSD Treatment

File this under ‘hidden clinical trial disorder.’ For a decade, the US military regularly prescribed its service members atypical antipsychotics, which are approved to treat schizophrenia and bipolar disorder, for various off-label uses, notably insomnia and post-traumatic stress disorder. And the antipsychotic that was most widely prescribed has been the Seroquel pill, which is sold by AstraZeneca (AZN).

For instance, a 2009 review of off-label use in the Veterans Affairs health care system found that 60 percent of patients who received an antipsychotic had no record of a diagnosis for which these drugs are approved. The largest proportion of prescriptions for off-label use was written for PTSD and Seroquel had the greatest off-label use (see this).

Last year, the armed services issued more than 54,500 prescriptions for Seroquel alone, which was, by far, the most for any antipsychotic (see Pharma news). And by 2009, Seroquel became the VA’s second-biggest pharmaceutical expenditure, reaching $125.4 million, up from $14.4 million in 2001.

This off-label use occurred even though VA clinical guidelines issued in 2004 stated that “there is insufficient evidence to recommend atypical antipsychotics for the treatment of PTSD.” By 2010, though, the VA guidelines were recommending atypical antipsychotics for augmented therapy, reflecting various small studies that indicated the pills were useful in treating symptoms.

By 2008, however, AstraZeneca was aware of at least one study that indicated Seroquel – when added to an existing therapy – was no better than a placebo in reducing PTSD symptoms, and 65 percent of the participants experienced side effects related to the drug. But the study, which was sponsored by the drug maker, was never published and a VA spokeswoman says the agency was not aware of its existence. At some point, however, the results were posted on the AstraZeneca web site (here it is).

The disclosure comes amid a growing controversy over hidden clinical trial data that has plagued the pharmaceutical industry. In recent years, scandals over undisclosed data linked to serious side effects involved Merck (MRK) and its Vioxx painkiller, as well as the Avandia diabetes pill sold by GlaxoSmithKline (GSK). In fact, Glaxo recently pledged to make data available after paying a $3 billion fine, in part, for failing to release some Avandia data (read Pharma news).

The failure to disclose the Seroquel study prompts concern, experts say, not only because AstraZeneca failed to make the findings known, but because antipsychotics have been linked to irregular heartbeats. For instance, a 2009 study in The New England Journal of Medicine found the rate of sudden cardiac death doubled for those taking atypical antipsychotics, and there were three such deaths each year for every 1,000 patients taking such a drug (here is the abstract). The Seroquel study says that electrocardiagrams were taken, but there is no mention of any findings.

For these reasons, industry critics say the Seroquel study is only the latest example of a clinical trial result that should have been publicized, especially given what was growing use in the military for an unapproved purpose. “This seems to be important and useful information that should be publicly known,” says Yale University cardiologist Harlan Krumholz, who has pushed for greater disclosure (read this). “It speaks to the importance of the totality of data being available for public scrutiny.”